Prevalence of Asthma and Asthma-like Symptoms: a Study in Five Provinces of Iran

Background: Asthma is a complex chronic inflammatory airway disease affecting millions of people worldwide. The prevalence of asthma attacks in most regions of the world, including the developing countries, increases due to urbanization, industrialization, and lifestyle. Materials and Methods: The present study aimed at investigating the prevalence of asthma and asthma symptoms in five provinces of Iran using the stratified cluster sampling method and the European Community Respiratory Health Survey (ECRHS) questionnaire. Results: A total of 4918 subjects were enrolled in the study. The prevalence of nocturnal cough was 27.4% (95% confidence interval (CI): 26%–28%); it was the most common asthma symptom followed by nocturnal shortness of breath (19.6%; 95%CI: 18–21%). For participants aged 20–44 years, the most prevalent symptoms were coughing attacks (37.7%), shortness of breath (26.5%), and nasal allergies (22.7%), respectively. Conclusion: There was a significant association among gender, age, and nasal allergy. Relevant studies should be conducted to figure out the countrywide distribution and the real burden of the disease.


INTRODUCTION
Asthma is a complex chronic inflammatory airway disease affecting millions of people worldwide. The overall prevalence of asthma is difficult to estimate precisely, ranging from 1% to 20% using different case definitions for both children and adults (1,2). According to the Global Asthma Report, the prevalence of asthma attacks and treatment for asthma increase in most regions of the world including the developing countries due to urbanization, industrialization, lifestyle, increased awareness of wheeze and wheeze-related symptoms, and also in response to international guidelines for asthma treatment during the 1990s (3,4). Evaluation of asthma usually involves a combination of signs and symptoms, including patients' medical history, physical examination, and lung function test. Clinical definitions given in questionnaires are usually used in prevalence studies (5)(6)(7)(8).

Shokouhi et al., in a cross sectional study on 2569 subjects
reported the prevalence of asthma as 7.6% (9). Tazesh et al., in a survey in Tehran, revealed that 10.8% of inhabitants aged 20-44 years had asthma (wheezing and breathlessness) (10). In two other studies conducted in Mashhad and Urmia, the prevalence of asthma symptoms was less than the reported figures (11,12). In the authors' previous study in Tehran (2016), using the European Community Respiratory Health Survey (ECRHS) questionnaire, 6.7% of participants had wheezing and breathlessness (13) A meta-analysis by Masjedi et al., evaluated articles published on asthma using data from 23 countries of EMRO. They reported a 7.95% prevalence of asthma in Iran that was lower than those of Kuwait, Qatar, and Saudi Arabia in the region (14).
The ECRHS is wildly used in different regions to address asthma epidemiology in adults (6,15). The ECRHS was the first study to assess the status of asthma in adults in 25 countries in three phases in terms of geographical prevalence, risk factors, treatment, and follow-up (5,16,17). The questionnaire is now one of the most popular instruments for epidemiologic studies due to its high validity and acceptability. It contains 10 general and specific questions used in large-scale surveys of asthma. It is advantageous to study asthma distribution and prevalence using the same instruments and definitions, including comparison with other studies, accurate estimation of the burden of the disease, and formulation of appropriate prevention policies.
The present study aimed at investigating the prevalence of asthma using the ECRHS questionnaire and measuring the prevalence of asthma symptoms among adults aged 20 to 44 years in five provinces of Iran.

Population and sampling strategy
The current population-based, cross sectional study was conducted to assess the frequency of asthma and asthma symptoms in five provinces of Iran with 28.7 million populations, nearly one-third of the Iran population. In the current study, the country was divided into five geographical areas: North, East, West, South, and Center. The stratified cluster sampling method was used considering urban areas and the density of the population in each city.
Sample Size: According to the authors' previous study, (13) considering the study power of at least 80%, the effect size of 1.5, and the response rate of 60%, the sample size was calculated 961. The sample size was determined 3366 to obtain accurate results. Finally, 4918 subjects were enrolled in the study. First, the participants were assigned to three age groups, including <20, 20-39, and >40 years in order to evaluate demographic characteristics, frequency of relevant symptoms, and medical history. Then, the participants were studied if they were in the age range of 20 to 44 years, considering mandatory standards in ECRHS screening. In order to minimize the misclassification regarding chronic obstructive pulmonary diseases (COPD), spirometry data were collected, which expanded the population age range beyond ECRHS to some extent.
The stratification was performed considering municipal districts of the administrative center of provinces.
Appreciating the population density in different districts, the appropriate number of clusters was weighted for each district. The number was also affected by the total sample size, the average number of members per household, logistics facilities for subject enumeration, transport, and examination. There were three-member teams to interview with the clusters in order to obtain data. Two interviewers, a man and a woman dressed in white medical coats, and a driver were recruited. The interviewing team approached the index household specified via the random selection of clusters and continued the enumeration in 10 neighboring households in a systematic manner by proceeding in a clockwise direction. The interviewers were advised to try the Kish grid to select the right participant(s) when there was more than one member in the indexed household. The Kish grid is a table of numbers used to find the number of residents in the household. Then, a randomly selected number determines the interviewee.
Definition: Two definitions used in previous studies on asthma prevalence were retrieved. Asthma symptoms in the study were considered based on the following definitions: 1. ECRHS (15,19), which implies possible asthma: Woken up by breathlessness attacks, history of an asthma attack, or currently taking asthma medications within the preceding 12 months.

Modified ECRHS: (20) Presence of the symptoms
wheezing or whistling, shortness of breath attack, diagnosed asthma attack in the past 12 months, or currently taking medicines for asthma.
Current asthma was defined as affirmative answers to each of the following questions: "Have you ever had asthma?" followed by "Was this confirmed by a doctor?", and "Have you had at least one asthma symptom in the past 12 months?" (5). If a respondent was diagnosed with asthma by a physician and experienced asthma symptoms in the past 12 months, he/she was defined as currently having asthma.
Examination protocol and questionnaire: The main instrument to estimate the prevalence of asthma and asthma symptoms was the ECRHS questionnaire (16) previously used in similar domestic studies (11). The ECRHS questionnaire is the standard tool used in the survey of the European Respiratory Society at 48 centers in 17 European countries and five non-European countries from 1990 to 1995 in adults aged 20-44 (16). Backtranslation from Farsi into English version was performed to confirm the questionnaire's validity.
All questionnaires were filled out by interviewers. To evaluate asthma symptoms, the same questions included in the ECRHS were asked.

Statistical analysis
Frequency tables, including number and percentage, were used for qualitative variables and mean and standard deviation (SD) were also employed for continuous variables. The prevalence was reported as a proportion,
Prevalence of asthma symptoms according to modified

ECRHS:
The asthma symptoms are presented in Table 2. The most prevalent symptom was nasal allergies (29.5%), followed by a coughing attack (27.4%), and shortness of breath (19.6%). Also, the asthma symptoms were stratified by age; symptoms among the age groups were significantly different (P <0.05).
In these subjects, females were older than males with the The number of participants in the 20-39 years age group was greater than those of the other age groups (P <0.001).
The prevalence of asthma symptoms by gender for the ones who answered YES is shown in Table 3. Coughing attack (58.9%), nasal allergies (47.5%), and wheezing (39.1%) were the most prevalent symptoms, respectively.
The coughing attack was also the most prevalent symptom in stratifying by gender. The prevalence of males and females was 38.9% and 36.2%, respectively. The prevalence of wheezing and shortness of breath was significantly different between males and females (P <0.05) ( Table 4).

Figures 1 and 2 indicate the trend in wheezing and
breathlessness by age and gender. The prevalence of wheezing for males increased up to 30% and then decreased for older participants; for females, wheezing increased up to 40% and then showed a decreasing trend.
The prevalence of shortness of breath was higher among females than males, based on age.

Factors associated with asthma symptoms according to ECRHS and modified ECRHS screening:
According to ECRHS screening, gender, and a history of nasal allergy had statistically significant relationships with asthma symptoms. The chance of asthma for females was higher than that of males (odds ratio (OR): 1.34; 95%CI: 1.15-1.57). Also, the chance of asthma for subjects with nasal allergy was 69% more than that of the ones without nasal allergy (OR: 1.69; 95%CI: 1.42-2.02).
For modified ECRHS, the history of nasal allergy was the only factor associated with asthma symptoms (OR: 2.65; 95%CI: 1.92-3.66), and the chance of asthma was twice more for patients with allergy than the ones with no allergic reactions (Table 5).  Table 3. Characteristics of those responding "YES" to Q1 "wheezing", Q4 "coughing", Q5 "asthma", or Q7 "nasal allergies" according to the ECRHS screening questionnaire (n =2169) Though the proposition cannot be extended to current asthma, wheezing could manifest itself as the crucial symptom of asthma in early adulthood. These findings verified and extended the reports of some studies suggesting a gradual change in the relative prevalence of asthma in males and females between the pubertal years and early adulthood (30)(31)(32).
The present study evaluated the risk of asthma symptoms associated with age, gender, history of nasal allergy, and cigarette smoking in a population-based setting. The chance of asthma symptoms significantly differed between males and females, which might be due to a different number of male and female subjects included in the study. As discussed earlier, the reasons underlying the distinctive gender differences need further investigation. Also, the prevalence of asthma among subjects with nasal allergy was 69% higher than that of the ones without it. This finding was in agreement with those of the other studies that observed a clear association between nasal allergy and asthma or asthma symptoms (20,33). Desalu  The main strengths of the study were the large and representative sample size and the use of a standardized and validated screening questionnaire. In addition, a rigorous sampling method was used, and the response rate was high.

CONCLUSION
In conclusion, according to the findings of the current study, the prevalence of asthma symptoms was considerably high in the five largest provinces of Iran in comparison with those of other countries. Moreover, there was a significant association among gender, age, and nasal allergy. Relevant studies should be conducted to